Molecular Printboards: Monolayers of β-Cyclodextrins on Silicon

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Molecular Printboards: Monolayers of β-Cyclodextrins on Silicon Oxide Surfaces Steffen Onclin, Alart Mulder, Jurriaan Huskens, Bart Jan Ravoo,* and David N. Reinhoudt* Supramolecular Chemistry and Technology, MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands Received February 19, 2004. In Final Form: April 16, 2004 Monolayers of β-cyclodextrin host molecules have been prepared on SiO2 surfaces. An ordered and stable cyano-terminated monolayer was modified in three consecutive surface reactions. First, the cyanide groups were reduced to their corresponding free amines using Red Al as a reducing agent. Second, 1,4-phenylene diisothiocyanate was used to react with the amine monolayer where it acts as a linking molecule, exposing isothiocyanates that can be derivatized further. Finally, per-6-amino β-cyclodextrin was reacted with these isothiocyanate functions to yield a monolayer exposing β-cyclodextrin. All monolayers were characterized by contact angle measurements, ellipsometric thickness measurements, Brewster angle Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry, which indicate the formation of a densely packed cyclodextrin surface. It was demonstrated that the β-cyclodextrin monolayer could bind suitable guest molecules in a reversible manner. A fluorescent molecule (1), equipped with two adamantyl groups for complexation, was adsorbed onto the host monolayer from solution to form a monolayer of guest molecules. Subsequently, the guest molecules were desorbed from the surface by competition with increasing β-cyclodextrin concentration in solution. The data were fitted using a model. An intrinsic binding constant of 3.3 ( 1 × 105 M-1 was obtained, which corresponds well to previously obtained results with a divalent guest molecule on β-cyclodextrin monolayers on gold. In addition, the number of guest molecules bound to the host surface was determined, and a surface coverage of ca. 30% was found.

Introduction Self-assembled monolayers1,2 (SAMs) offer a unique way to confine molecules in two dimensions. When functionalized with suitable receptor adsorbates, SAMs can be used to monitor binding events at the interface. In addition, a chemisorbed layer of host molecules can act as a template onto which guest molecules can be immobilized. In principle, this opens the way to build multilayered supramolecular architectures, based upon specific recognition reactions, in a controlled fashion.3 Several supramolecular recognition motifs have been used where an immobilized organic layer binds guest molecules reversibly. These motifs include crown ether complexation by ammonium SAMs,4,5 His-tagged proteins by a Ni-nitrilotriacetic acid presenting surface,6,7 and adamantyl complexation by cyclodextrin SAMs.8-10 We have recently introduced the term “molecular printboard”9 for a host surface onto which guest molecules can be positioned by reversible interactions of tunable strength. * To whom correspondence should be addressed. Fax: +31 53 4894645. Phone: +31 53 4892980. E-mail: [email protected]; [email protected]. (1) Ulman, A. An Introduction to Ultrathin Organic Films; Academic Press: Boston, 1991. (2) Ulman, A. Chem. Rev. 1996, 96, 1533-1554. (3) Spinke, J.; Liley, M.; Guder, H. J.; Angermaier, L.; Knoll, W. Langmuir 1993, 9, 1821-1825. (4) Arias, F.; Godinez, L. A.; Wilson, S. R.; Kaifer, A. E.; Echegoyen, L. J. Am. Chem. Soc. 1996, 118, 6086-6087. (5) Miura, Y.; Kimura, S.; Imanishi, Y.; Umemura, J. Langmuir 1998, 14, 2761-2767. (6) Dietrich, C.; Schmitt, L.; Tampe, R. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9014-9018. (7) Thess, A.; Hutschenreiter, S.; Hofmann, M.; Tampe, R.; Baumeister, W.; Guckenberger, R. J. Biol. Chem. 2002, 277, 36321-36328. (8) Fragoso, A.; Caballero, J.; Almirall, E.; Villalonga, R.; Cao, R. Langmuir 2002, 18, 5051-5054. (9) Huskens, J.; Deij, M. A.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 2002, 41, 4467-4471.

A well-known class of receptor molecules are cyclodextrins that consist of six (R), seven (β), or eight (γ) R-D-glucose units. These macrocycles are water-soluble molecules that contain a hydrophobic cavity, which enables complexation of organic molecules from aqueous solutions based on hydrophobic interactions. Immobilization of cyclodextrins (CDs) on gold surfaces and the complexation behavior of immobilized CDs has been a topic of research for a number of years. Kaifer and co-workers have synthesized per-6-thio-β-cyclodextrins which chemisorb onto gold surfaces forming at least 6 S-Au bonds per β-CD.11-13 They found that imperfect monolayers were formed, so a treatment with pentanethiol was used to cover the defects. Interfacial ferrocene complexation was demonstrated by competition experiments with m-toluic acid (mTA). To increase the lateral mobility of the CDs during the chemisorption process, the number of sulfur moieties per CD has to be decreased. Mittler-Neher and co-workers immobilized a number of mono- and multithiolated CDs and found that the adsorption kinetics can be described by a three-step process: a physisorption process, a binding and orientation step, and an adlayer formation.14-16 Galla and co-workers have studied monolayers of CDs on gold surfaces and at the air-water (10) Auletta, T.; Dordi, B.; Mulder, A.; Sartori, A.; Onclin, S.; Bruinink, C. M.; Pe´ter, M.; Nijhuis, C. A.; Beijleveld, H.; Scho¨nherr, H.; Vancso, G. J.; Casnati, A.; Ungaro, R.; Ravoo, B. J.; Huskens, J.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 2004, 43, 369-373. (11) Rojas, M. T.; Koniger, R.; Stoddart, J. F.; Kaifer, A. E. J. Am. Chem. Soc. 1995, 117, 336-343. (12) Kaifer, A. E. Isr. J. Chem. 1996, 36, 389-397. (13) Kaifer, A. E. Acc. Chem. Res. 1999, 32, 62-71. (14) Nelles, G.; Weisser, M.; Back, R.; Wohlfart, P.; Wenz, G.; MittlerNeher, S. J. Am. Chem. Soc. 1996, 118, 5039-5046. (15) Weisser, M.; Nelles, G.; Wohlfart, P.; Wenz, G.; Mittler-Neher, S. J. Phys. Chem. 1996, 100, 17893-17900. (16) Weisser, M.; Nelles, G.; Wenz, G.; Mittler-Neher, S. Sens. Actuators, B 1997, 38, 58-67.

10.1021/la049561k CCC: $27.50 © 2004 American Chemical Society Published on Web 05/25/2004

Molecular Printboards

interface.17-19 SAMs of mercaptopropane-N-mono-6-deoxyβ-cyclodextrin amide were found to form with a surface coverage of 99-100%. In addition, they investigated complexation behavior of the SAMs by means of impedance spectroscopy and demonstrated that the binding process of guests is reversible by the addition of excess CD in solution.18 Our group has reported the immobilization of several receptor adsorbates,20-24 including cyclodextrins.9,10,25-31 The strategy to obtain dense, well-packed monolayers consists of filling the space underneath the receptor headgroup by alkyl chains and using multiple attachment points.26 Modifying β-CDs with seven dialkyl sulfide moieties resulted in ordered layers as revealed by high-resolution atomic force microscopy (AFM). A quasi-hexagonal lattice with a lattice constant of 20.6 Å was found, which matches the geometry of the adsorbate.27 Monolayers of these β-CD adsorbates on gold were characterized by electrochemistry, wettability studies, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), and AFM. The β-CD SAMs have been used for complexation with organic guests, where it was found that they show the same selectivity and binding strength as β-CD in solution.28 The β-CD SAMs have also been applied in single molecule force spectroscopy measurements, where pulloff forces of individual host-guest complexes were quantified.29-31 Recently, we introduced the concepts of supramolecular microcontact printing and supramolecular dip-pen nanolithography, where the β-CD SAMs were used to reversibly create patterns with a variety of multivalent guest molecules.10 An inherent disadvantage when working with SAMs on gold is the difficulty in using fluorescence techniques. The reason for this is that the excited state of fluorescent molecules situated at or near the gold couples with the surface plasmons of the gold, resulting in energy transfer from the fluorescent dye to the surface without emission. This quenching process is a well-known phenomenon for (17) Henke, C.; Steinem, C.; Janshoff, A.; Steffan, G.; Luftmann, H.; Sieber, M.; Galla, H. J. Anal. Chem. 1996, 68, 3158-3165. (18) Michalke, A.; Janshoff, A.; Steinem, C.; Henke, C.; Sieber, M.; Galla, H. J. Anal. Chem. 1999, 71, 2528-2533. (19) Janshoff, A.; Steinem, C.; Michalke, A.; Henke, C.; Galla, H. J. Sens. Actuators, B 2000, 70, 243-253. (20) Schierbaum, K. D.; Weiss, T.; Thoden van Velzen, E. U.; Engbersen, J. F. J.; Reinhoudt, D. N.; Gopel, W. Science 1994, 265, 1413-1415. (21) Thoden van Velzen, E. U.; Engbersen, J. F. J.; Delange, P. J.; Mahy, J. W. G.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 68536862. (22) Friggeri, A.; Van Veggel, F.; Reinhoudt, D. N.; Kooyman, R. P. H. Langmuir 1998, 14, 5457-5463. (23) Flink, S.; Boukamp, B. A.; Van den Berg, A.; Van Veggel, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1998, 120, 4652-4657. (24) Flink, S.; Van Veggel, F.; Reinhoudt, D. N. J. Phys. Chem. B 1999, 103, 6515-6520. (25) De Jong, M. R.; Huskens, J.; Reinhoudt, D. N. Chem.sEur. J. 2001, 7, 4164-4170. (26) Beulen, M. W. J.; Bugler, J.; Lammerink, B.; Geurts, F. A. J.; Biemond, E.; van Leerdam, K. G. C.; Van Veggel, F.; Engbersen, J. F. J.; Reinhoudt, D. N. Langmuir 1998, 14, 6424-6429. (27) Beulen, M. W. J.; Bugler, J.; De Jong, M. R.; Lammerink, B.; Huskens, J.; Scho¨nherr, H.; Vancso, G. J.; Boukamp, B. A.; Wieder, H.; Offenha¨user, A.; Knoll, W.; Van Veggel, F.; Reinhoudt, D. N. Chem.s Eur. J. 2000, 6, 1176-1183. (28) De Jong, M. R. Cyclodextrins for Sensing: Solution, Surface, and Single Molecule Chemistry. Ph.D. Thesis, University of Twente, Enschede, The Netherlands, 2001. (29) Scho¨nherr, H.; Beulen, M. W. J.; Bugler, J.; Huskens, J.; Van Veggel, F.; Reinhoudt, D. N.; Vancso, G. J. J. Am. Chem. Soc. 2000, 122, 4963-4967. (30) Zapotoczny, S.; Auletta, T.; De Jong, M. R.; Scho¨nherr, H.; Huskens, J.; Van Veggel, F.; Reinhoudt, D. N.; Vancso, G. J. Langmuir 2002, 18, 6988-6994. (31) Auletta, T.; De Jong, M. R.; Mulder, A.; Van Veggel, F. C. J. M.; Huskens, J.; Reinhoudt, D. N.; Zou, S.; Zapotoczny, S.; Scho¨nherr, H.; Vancso, G. J.; Kuipers, L. J. Am. Chem. Soc. 2004, 126, 1577-1584.

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fluorescent molecules near metallic surfaces,32,33 and for this reason fluorescence imaging is typically limited to oxide surfaces (e.g., SiO2). Fluorescence spectroscopy and microscopy can be very sensitive characterization tools that allow for both qualitative and quantitative analysis of binding processes at the surface.34 Therefore, to study interactions at β-CD monolayers by means of fluorescent techniques, the preparation of β-CD SAMs on SiO2 is required. Since their discovery in the early 1980s,35 SAMs of trichloro- and trialkoxysilanes on hydroxyl-terminated surfaces (e.g., glass, oxidized silicon wafers) have been investigated extensively.1,2 However, the high reactivity of the trichloro- and trialkoxysilanes strongly limits the number of functional groups that can be directly introduced into these SAMs. As a result, the chemical diversity of these monolayers has been rather limited when compared to that of SAMs on gold.36 In accordance with the limited number of functional groups available on the glass surface, reports on the immobilization of CD molecules are rare. Li and co-workers have reported the covalent binding of CDs to the SiO2 surface by using 1,6bis(trichlorosilyl)hexane as a coupling layer.37,38 However, hardly any characterization of these layers was given, and it is unlikely that ordered monolayers are formed as 1,6-bis(trichlorosilyl)hexane can backfold to react twice with the surface and is prone to form multilayers by polymerization. Attenuated total reflection infrared (ATRIR) measurements suggested the successful attachment of functionalized CDs, and interactions of the layers with volatile organic compounds (VOCs) in the gas phase were studied by surface acoustic wave (SAW) measurements. Modifying CDs with trialkoxysilanes on both the primary and secondary side led to deposition of CD siloxane multilayer thin films.39 Also, these films were used to monitor interactions with VOCs. CDs with an unmodified secondary side were immobilized by Busse and co-workers, who reacted per-6-amino β-cyclodextrin with an epoxyterminated monolayer.40 No characterization of the monolayer was performed, and the progress of the surface reaction was only monitored by an integrated optical MachZehnder interferometer. Host-guest interactions with adamantanecarboxylic acid, m-toluic acid, and methyl orange were investigated. In a recent communication, we reported that SAMs of β-CDs on SiO2 can be reversibly patterned by supra(32) (a) Chance, R.; Prock, A.; Silbey, R. Adv. Chem. Phys. 1978, 37, 1-65. (b) Enderlein, J. Chem. Phys. 1999, 247, 1-9. (c) Ku¨mmerlen, J.; Leitner, A.; Brunner, H.; Aussenegg, F. R.; Wokaun, A. Mol. Phys. 1993, 80, 1031-1046. (d) Reese, S.; Fox, M. A. J. Phys. Chem. B 1998, 102, 9820-9824. (33) Quenching especially hampers fluorescence at continuous metallic films but is less predominant at metallic nanoparticles or islands; see for example: (a) Chan, V. C. H.; Codd, S. L.; Van der Helm, M.; Spatz, J. P.; Ro¨cker, C.; Nienhaus, G. U.; Levi, S. A.; Van Veggel, F. C. J. M.; Reinhoudt, D. N.; Mo¨ller, M. J. Mater. Res. 2001, 676, Y4.4. (b) Levi, S. A.; Mourran, A.; Spatz, J. P.; Van Veggel, F. C. J. M.; Reinhoudt, D. N.; Mo¨ller, M. Chem.sEur. J. 2002, 8, 3808-3814. (c) Dulkeith, W.; Morteani, A. C.; Niedereichholtz, T.; Klar, T. A.; Feldmann, J.; Levi, S. A.; Van Veggel, F. C. J. M.; Reinhoudt, D. N.; Mo¨ller, M.; Gittins, D. I. Phys. Rev. Lett. 2002, 89, 203002, 1-3. (d) Chumanov, G.; Sokolov, K.; Gregory, B. W.; Cotton, T. M. J. Phys. Chem. 1995, 99, 9466-9471. (34) Yang, T. L.; Baryshnikova, O. K.; Mao, H. B.; Holden, M. A.; Cremer, P. S. J. Am. Chem. Soc. 2003, 125, 4779-4784. (35) Sagiv, J. J. Am. Chem. Soc. 1980, 102, 92-98. (36) Sullivan, T. P.; Huck, W. T. S. Eur. J. Org. Chem. 2003, 17-29. (37) Moore, L. W.; Springer, K. N.; Shi, J. X.; Yang, X. G.; Swanson, B. I.; Li, D. Q. Adv. Mater. 1995, 7, 729-731. (38) Li, D. Q.; Ma, M. Sens. Actuators, B 2000, 69, 75-84. (39) Yang, X.; Shi, J.; Johnson, S.; Swanson, B. Sens. Actuators, B 1997, 45, 79-84. (40) Busse, S.; DePaoli, M.; Wenz, G.; Mittler, S. Sens. Actuators, B 2001, 80, 116-124.

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Scheme 1. Synthesis Scheme for the Preparation of β-CD SAMs on SiO2 Surfacesa

a

(i) Red Al, toluene, 40 °C; (ii) DITC, toluene, 50 °C; (iii) per-6-amino β-CD, H2O, 50 °C.

molecular microcontact printing and how such patterns can be readily visualized by confocal fluorescence microscopy.10 Here we report the synthesis and detailed characterization of β-CD monolayers on SiO2 surfaces. The starting point was the formation of a stable SAM, followed by three consecutive surface reactions to introduce the β-CD host molecules. All surface reactions were monitored by a variety of analytical techniques including contact angle goniometry, ellipsometry, Brewster angle Fourier transform infrared (FT-IR) spectroscopy, XPS, and TOF-SIMS. In addition, binding studies between a fluorescent guest molecule and the host SAMs were performed. Experimental Details General Procedures. All moisture-sensitive reactions were carried out under a nitrogen atmosphere. Reagents were commercial and used without further purification. Four-inch polished, 100-cut, p-doped silicon wafers, cut into 2 × 2 cm samples, and microscope glass slides were used for monolayer preparation. Prior to monolayer formation, the substrates were oxidized by immersion in boiling piran˜a (H2SO4 (96%)/H2O2 (30%), 3: 1 v/v) for 15 min, rinsed with large amounts of Millipore water, and dried in a stream of nitrogen. Caution: piran˜a is a very strong oxidant and reacts violently with many organic materials. Contact angles were measured on a Kru¨ss G10 contact angle measuring instrument, equipped with a CCD camera. Advancing and receding contact angles were determined automatically during growth and shrinkage of the droplet by a drop shape analysis routine. Ellipsometric layer thickness measurements were performed on a Plasmos ellipsometer (λ ) 633 nm) assuming a refractive index of 1.500 for the monolayers and 1.457 for the underlying native oxide. The thickness of the SiO2 layer was measured separately on an unmodified part of the same wafer and subtracted from the total layer thickness determined for the monolayer-covered silicon substrate. Brewster angle infrared spectra were recorded on a Biorad FTS 60A spectrophotometer, equipped with a home-built nitrogen-purged glovebox in which the sample holder and MCT detector were situated. Spectra were recorded at an angle of incidence of 73.7° for 512 scans at a resolution of 4 cm-1. A background spectrum was first recorded using a freshly cleaned silicon substrate. TOF-SIMS spectra were acquired at Tascon GmbH (Mu¨nster, Germany) with an IONTOF “TOF-SIMS IV” instrument with a pulsed primary beam of Au1+ and Au3+ ions (25 keV) under static conditions. Spectra were taken from an area of 100 × 100 µm2 for positively and negatively charged secondary ions. XPS spectra were obtained on a Quantera Scanning X-ray Multiprobe instrument, equipped with a monochromatic Al KR X-ray source producing approximately 25 W of X-ray power. Spectra were referenced to the main C 1s peak set at 284.0 eV. XPS data were collected from

a surface area of 1000 µm × 300 µm with a pass energy of 224 eV and a step energy of 0.8 eV for survey scans and 0.4 eV for high-resolution scans. For quantitative analysis, the sensitivity factors used to correct the number of counts under each peak were as follows: C 1s, 1.00; N 1s, 1.59. AFM measurements were carried out with a Nanoscope III multimode AFM in tapping mode using Si3N4 cantilevers (purchased from Nanosensors) with a spring constant of 37-56 N m-1. Images were acquired in ambient atmosphere. Fluorescence spectroscopy was performed on an Edinburgh FS900 fluorospectrophotometer in which a 450 W xenon arc lamp was used as the excitation source. M300 gratings with 1800 1/mm were used on both excitation and emission arms. Signals were detected by a Peltier element cooled, red sensitive, Hamamatsu R928 photomultiplier system. Quartz sample cells of 1 mm were used. Monolayer Preparation. Substrates were exposed to a cooled (3-7 °C) 0.1 vol % solution of 1-cyano-11-trichlorosilylundecane (purchased from Gelest Inc.) in freshly distilled toluene for 35 min under N2. Following monolayer formation, the substrates were rinsed with toluene to remove any excess of silanes and subsequently dried in a stream of nitrogen. Surface Reactions. The cyano-terminated SAMs were reduced to the corresponding amines by immersion for 4 h in a 10 vol % solution of Red Al in toluene under a nitrogen atmosphere at 40 °C. Following the reduction, the substrates were sonicated in a 1 M HCl solution for 5 min to remove the Al salts and sonicated in a 0.5 M NaOH solution for 1 min to deprotonate the amines.41 The layers were further sonicated in and rinsed with large amounts of Millipore water and finally dried in a stream of nitrogen. Transformation of the amine-terminated SAMs to isothiocyanate-bearing layers was accomplished by exposure to a 0.1 M solution of 1,4-phenylene diisothiocyanate in toluene at 50 °C for 2 h under N2, followed by rinsing with toluene and drying in a stream of nitrogen. β-CD-terminated SAMs were finally obtained by reaction of the isothiocyanate-terminated monolayers with per-6-amino-β-cyclodextrin.42 The reaction was performed in an aqueous 5 mM per-6-amino-β-cyclodextrin solution (pH 8.5) at 50 °C for 2 h, after which the substrates were sonicated in Millipore water and finally rinsed with copious amounts of Millipore water to remove physisorbed material.

Results and Discussion Synthesis. The synthesis route to prepare β-CD SAMs on SiO2 is outlined in Scheme 1. It starts with the formation of a cyano-terminated monolayer of 1-cyano-11-trichlorosilylundecane. SAMs were prepared on cleaned microscope glass slides or silicon wafers by immersion of the substrate (41) Lee, M. T.; Ferguson, G. S. Langmuir 2001, 17, 762-767. (42) Ashton, P. R.; Koniger, R.; Stoddart, J. F.; Alker, D.; Harding, V. D. J. Org. Chem. 1996, 61, 903-908.

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Table 1. Advancing (θa) and Receding (θr) Water Contact Angles, Ellipsometric Thicknesses, and Selected XPS Data of SAMs Shown in Scheme 1 SAM

θa (deg)

θr (deg)

ellipsometric thickness (nm)

C/N (XPS)

C/N (calcd)

CN NH2 SCN β-CD

73 ( 1 60 ( 1 68 ( 1 49 ( 1

60 ( 2 25 ( 2